Ethylenediamine → HCID 71288925, compound

Reaction equation

[C:1]([C@H:3]1[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[N:14](COCC[Si](C)(C)C)[CH:13]=2)=[O:11])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([C@H:3]1[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[NH:14][CH:13]=2)=[O:11])[CH2:4]1)#[N:2]

Participants

Procedure

In a 25 mL round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-cyanocyclohexyl)-amide (48 mg, 0.085 mmol) was dissolved in dichloromethane (3 mL). Trifluoroacetic acid (1.2 mL, 15.6 mmol) was added and the orange reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (3 mL) and ethylenediamine (0.50 mL, 7.4 mmol) was added. The light yellow reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was sequentially washed with water, ethyl acetate, and hexanes to afford 35 mg (95%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-cyanocyclohexyl)-amide as an off-white solid. MS: [M+Na]+=474; 1H NMR (DMSO-d6) δ: 12.79 (br. s., 1H), 9.08 (s, 1H), 8.46 (s, 1H), 8.40 (d, J=8.7 Hz, 1H), 8.08 (d, J=7.9 Hz, 1H), 8.00 (d, J=0.8 Hz, 1H), 7.37 (dd, J=8.5, 1.1 Hz, 1H), 4.17 (s, 3H), 4.01-4.31 (m, 1H), 3.30-3.49 (m, 1H), 2.24 (d, J=13.2 Hz, 1H), 2.07 (d, J=12.1 Hz, 1H), 1.59-1.94 (m, 5H), 1.36-1.59 (m, 1H).